This application is for continued support of our ongoing broad program of research on the biochemical characterization of neoplastic tissues, encompassing the following specific problems. 1. A study of isozyme patterns and enzyme regulation in a series of transplantable rat hepatomas in relation to growth rate and degree of differentiation. This is a continuation of previous work, which points to re-expression in poorly differentiated hepatomas, of isozymes which were expressed during the fetal stage, but suppressed during normal embryonic development. Current work is focused on the nature and properties of isozymes of pyruvate kinase, carbamyl phosphate synthetase, creatine kinase and phosphoenolpyruvate carboxylase. 2. A combined immunochemical-radiochemical study of the rates of synthesis and degradation of phosphoenolpyruvate carboxykinase in a well differentiated hepatoma, the Reuber H-35, in cell culture and the influence thereon of insulin, cortisol, and cyclic AMP (with Drs. Richard W. Hanson and Martyn Gunn). 3. A kinetic study of the competition between pyruvate kinase and the mitochondrial respiratory system for ADP as a factor in the control of glycolysis in tumors (with Mario Gosalvez). 4. A comparative study of isozyme patterns of hexokinase, aldolase, glycogen phosphorylase and pyruvate kinase in cultured tumor cells and their solid tumor counterparts (with Martyn Gunn).